Novel drug isolated from mistletoe (1E,4E)-1,7-bis(4-hydroxyphenyl)hepta-1,4-dien-3-one for potential treatment of various cancers: synthesis, pharmacokinetics and pharmacodynamics
2020
Hong, Jing | Meng, Lin | Yu, Peipei | Zhou, Ceng | Zhang, Zhaoyan | Yu, Zhiguo | Qin, Feng | Zhao, Yunli
(1E,4E)-1,7-Bis(4-hydroxyphenyl)hepta-1,4-dien-3-one (DHDK) is a novel curcuminoid analogue isolated from mistletoe. DHDK exhibits better anti-tumour activity, higher bioavailability and superior stability than curcumin. DHDK is difficult to isolate from Viscum coloratum, but it can be synthesised. MTT (methylthiazolyldiphenyl tetrazolium bromide) assay was used to evaluate the in vitro cytotoxic activity of synthesised DHDK on 12 cancer cell lines. Results showed that DHDK exhibited excellent potential as an anticancer agent, especially for breast and lung cancer. Efficacy was further evaluated in vivo by using MCF-7 breast cancer models. DHDK showed a dose-dependent relationship without weight reduction, mortality growth inhibition or tissue toxicity. Pharmacokinetics and tissue distribution statistics were determined by LC-ESI-MS/MS. This work provided preliminary data on this natural compound and could open up new prospects for changing related parameters to improve drug efficacy.
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